| Co-Investigator(Kenkyū-buntansha) |
HIRATA Yasunobu University of Tokyo, Faculty of Medicine, Assistant Professor, 医学部(病), 助手 (70167609)
NAGAI Ryozo University of Tokyo, Faculty of Medicine, Associate Professor, 医学部(病), 助教授 (60207975)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
In the present study we demonstrated that the phenotypic modulation occurred in smooth muscles of renal arterioles and in glomerular cells during development of hypertension and various glomerular diseases. Salt-loaded stroke-prone-spontaneously hypertensive rats (SHRSP) developed malignant hypertension. In the kidney, the expression of SM2 (muscle-type myosin heavy chain isoform) and alpha-actin was decreased according to the degree of vascular damages. As SM2 is regarded to be expressed in highly differentiated smooth muscles of strong contractility, the decrease in SM2 expression might result in functional abnormalities in arterioles, which accelerates hypertensive glomerular damage. The mesangial cells expressed non-muscle myosin, Smemb, and alpha-actin. In various glomerular diseases, the phenotypic modulation took place in the epithelial cells and in the mesangial cells. These phenotypic modulations were confirmed by the immunoelectron microscopy and also by the northern analysis of messenger RNA.In the anti-thy-1 glomerulonephritis, mesangial cells express alpha-actin from the earlier stage of the disease and also Smemb in the later stage. In the remnant kidney, Smemb was expressed in the mesangial cells at the earlier stage, but in the epithelial cells at the later stage, when the glomerular hypertrophy developed. In the anti-glomerular basement membrane glomerulonephritis and the streptozotocin-induced diabetic kidney, both the epithelial and mesangial cells expressed Smemb. In the remnant kidney, the anti-GBM glomerulonephritis or diabetic kidney, alpha-actin was not expressed at all. Thus, the phenotypic modulation of glomerular cells took place heterogeneously as well as in the varying manner. At present, the functional meaning of the phenotypic modulation of glomerular cells is unknown.
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